7KWZ

TDP-43 LCD amyloid fibrils

7KWZ の概要

• エントリーDOI: 10.2210/pdb7kwz/pdb
• EMDBエントリー: 23059
• 分子名称: Isoform 2 of TAR DNA-binding protein 43 (1 entity in total)
• 機能のキーワード: tdp-43, amyloid, neurodegenerative diseases, amyotropic lateral sclerosis, protein fibril
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 72852.41

構造登録者

Li, Q.,Babinchak, W.M.,Surewicz, W.K. (登録日: 2020-12-02, 公開日: 2021-02-24, 最終更新日: 2024-03-06)

主引用文献

Li, Q.,Babinchak, W.M.,Surewicz, W.K.
Cryo-EM structure of amyloid fibrils formed by the entire low complexity domain of TDP-43.
Nat Commun, 12:1620-1620, 2021

PubMed Abstract: Amyotrophic lateral sclerosis and several other neurodegenerative diseases are associated with brain deposits of amyloid-like aggregates formed by the C-terminal fragments of TDP-43 that contain the low complexity domain of the protein. Here, we report the cryo-EM structure of amyloid formed from the entire TDP-43 low complexity domain in vitro at pH 4. This structure reveals single protofilament fibrils containing a large (139-residue), tightly packed core. While the C-terminal part of this core region is largely planar and characterized by a small proportion of hydrophobic amino acids, the N-terminal region contains numerous hydrophobic residues and has a non-planar backbone conformation, resulting in rugged surfaces of fibril ends. The structural features found in these fibrils differ from those previously found for fibrils generated from short protein fragments. The present atomic model for TDP-43 LCD fibrils provides insight into potential structural perturbations caused by phosphorylation and disease-related mutations.

PubMed: 33712624
DOI: 10.1038/s41467-021-21912-y

実験手法

ELECTRON MICROSCOPY (3.2 Å)